SCN1A rs6732655A/T polymorphism:Diagnostic and therapeutic insights for drug-resistant epilepsy  

作　　者：Aroop Viswas Pradeep K Dabla Dharmsheel Shrivastav Swapan Gupta Manisha Yadav Subhash Yadav Bidhan Chandra Koner 

机构地区：[1]Department of Biochemistry,Govind Ballabh Pant Institute of Postgraduate Medical Education and Research,New Delhi 110002,Delhi,India [2]Department of Neurology,Govind Ballabh Pant Institute of Postgraduate Medical Education and Research,New Delhi 110002,Delhi,India [3]Multi-disciplinary Research Unit,Maulana Azad Medical College,New Delhi 110002,Delhi,India [4]Department of Biotechnology,Amity University Gwalior,Gwalior 474005,Madhya Pradesh,India [5]Department of Biochemistry,Maulana Azad Medical College,New Delhi 110002,Delhi,India

出　　处：《World Journal of Experimental Medicine》2024年第3期72-79,共8页世界实验医学杂志

摘　　要：BACKGROUND A significant subset of individuals with epilepsy fails to respond to currently available antiepileptic drugs,resulting in heightened mortality rates,psychosocial challenges,and a diminished quality of life.Genetic factors,particularly within the SCN1A gene,and the pro-inflammatory cytokine response is important in intricating the drug resistance in idiopathic epilepsy cases.In this extended study,we determined the correlation of rs6732655A/T single nucleotide polymorphism to understand the causative association of SCN1A gene with epilepsy drug resistance and inflammatory response.AIM To find the correlation of SCN1A gene rs6732655A/T polymorphism with the drug-resistant epilepsy and inflammatory response.METHODS The study enrolled 100 age and sex-matched patients of both drug-resistant and drug-responsive epilepsy cases.We analysed the rs6732655A/T polymorphism to study its association and causative role in drug-resistant epilepsy cases using restriction fragment length polymorphism technique.The diagnostic performance of interleukin(IL)-1β,IL-6,and high mobility group box 1(HMGB1)protein levels was evaluated in conjunction with genotypic outcome receiver operating characteristic analysis.RESULTS AT and AA genotypes of rs6732655 SCN1A gene polymorphism were associated with higher risk of drug resistance epilepsy.Serum biomarkers IL-6,IL1βand HMGB1 demonstrated diagnostic potential,with cutoff values of 4.63 pg/mL,59.52 pg/mL and 7.99 ng/mL,respectively,offering valuable tools for epilepsy management.Moreover,specific genotypes(AA and AT)were found to be linked to the elevated levels of IL-1βand IL-6 and potentially reflecting increased oxidative stress and neuro-inflammation in drug-resistant cases supporting the previous reported outcome of high inflammatory markers response in drug resistance epilepsy.CONCLUSION SCN1A genotypes AA and AT are linked to higher drug-resistant epilepsy risk.These findings underscore the potential influence of inflammation and genetics on epilepsy treatment resistance

关 键 词：EPILEPSY Drug resistance SCN1A gene Pro-inflammatory cytokines Genetic factors 

分 类 号：R742.1[医药卫生—神经病学与精神病学]